cart-19 immunotherapy in mantle cell lymphoma

Conditions: Hematopoietic/Lymphoid Cancer; Non-hodgkin Lymphoma,B Cell; Mantle Cell Lymphoma

Summary: patients receive anti-cd19-car (coupled with cd137 and cd3 zeta signalling domains)vector-transduced autologous t cells over a period of 4 or 5 consecutive days in an escalating dose. after completion of study treatment, patients are followed intensively for 6 months, every 3 months for 2 years, and annually thereafter for 10 years.

primary objectives: i. determine the safety and efficacy of the chimeric antigen receptor t cells transduced with the anti-cd19 (cluster of differentiation antigen 19 ) vector (referred to as cart-19 cells) in elderly patients with mcl. ii. determine duration of in vivo survival of cart-19 cells. rt-pcr (reverse transcription polymerase chain reaction) analysis of whole blood will be used to detect and quantify survival of cart-19 tcr (t-cell receptor) zeta:cd137 and tcr zeta cells over time. secondary objectives: for patients with detectable disease, measure anti-tumor response due to cart-19 cell infusions. estimate relative trafficking of cart-19 cells to tumor in bone marrow and lymph nodes. determine if cellular or humoral host immunity develops against the murine anti-cd19, and assess correlation with loss of detectable cart-19 (loss of engraftment).

Eligibility criteria:
inclusion criteria: * male and female with cd19+ relapsed or refractory mcl, and with no available curative treatment options (such as autologous or allogeneic sct) who have limited prognosis (several months to \< 2 year survival) with currently available therapies will be enrolled. * not eligible or appropriate for conventional allogeneic sct * patients who achieve only a partial response to fcr(fludarabine, cyclophosphamide and rituxan) as initial therapy will be eligible. * beyond 1st cr (complete remission) with relapsed or persistent disease and not eligible or appropriate for conventional allogeneic or autologous sct * disease responding or stable after most recent therapy (chemotherapy, moab, etc...) * relapsed after prior autologous sct * residual disease after primary therapy and not eligible for autologous sct * relapsed after prior autologous sct * beyond 1st cr with relapsed or persistent disease and not eligible or appropriate of conventional allogeneic or autologous sct * expected survival \> 12 weeks * creatinine \< 2.5 mg/dl * alt(alanine aminotransferase)/ast (aspartate aminotransferase)\< 3x normal * bilirubin \< 2.0 mg/dl * any relapse after prior autologous sct will make patient eligible regardless of other prior therapy * adequate venous access for apheresis, and no other contraindications for leukapheresis * voluntary informed consent is given exclusion criteria: * • pregnant or lactating women. the safety of this therapy on unborn children is not known. female study participants of reproductive potential must have a negative serum or urine pregnancy test performed within 48 hours before infusion. * uncontrolled active infection * active hepatitis b or hepatitis c infection * concurrent use of systemic steroids. recent or current use of inhaled steroids is not exclusionary * previously treatment with any gene therapy products * feasibility assessment during screening demonstrates \< 30% transduction of target lymphocytes, or insufficient expansion (\< 5-fold) in response to cd3/cd137 costimulation * any uncontrolled active medical disorder that would preclude participation as outlined * hiv infection

Keywords: chimeric antigen receptor immunotherapy t lymphocyte mantle cell lymphoma